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  6. A Mesoporous Gold Sensor Unveils Phospho Pd-l1 In Extracellular Vesicles As A Proxy For Pd-l1 Expression In Lung Cancer Tissue

A Mesoporous Gold Sensor Unveils Phospho PD-L1 in Extracellular Vesicles as a Proxy for PD-L1 Expression in Lung Cancer Tissue

Karthik B Shanmugasundaram1, Emtiaz Ahmed1, Xinzhe Miao1

  • 1Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.

ACS Sensors
|June 5, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

A novel liquid biopsy assay measuring phosphorylated PD-L1 in extracellular vesicles (EV pPD-L1) accurately predicts tumor PD-L1 status in non-small-cell lung cancer (NSCLC). This rapid test can help select patients for immunotherapy, overcoming tissue biopsy limitations.

Area of Science:

  • Oncology
  • Biomarkers
  • Immunotherapy

Background:

  • Immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 improve survival in non-small-cell lung cancer (NSCLC).
  • Tissue biopsy for PD-L1 assessment is challenging, especially for achieving high scores (TPS ≥ 50%) needed for certain therapies.
  • Liquid biopsies offer a less invasive alternative for biomarker assessment.

Purpose of the Study:

  • To evaluate a mesoporous gold sensor (MGS) assay for detecting phosphorylated PD-L1 in plasma extracellular vesicles (EV pPD-L1) in NSCLC patients.
  • To correlate EV pPD-L1 levels with tumor PD-L1 tissue proportion score (TPS) determined by immunohistochemistry.
  • To assess the utility of EV pPD-L1 as a predictive biomarker for ICI therapy in NSCLC.

Main Methods:

  • Utilized a mesoporous gold sensor (MGS) assay for sensitive detection of PD-L1 in plasma extracellular vesicles (EV pPD-L1).
Keywords:
biosensingextracellular vesiclesinterfacial biosensingliquid biopsy

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  • Analyzed plasma PD-L1 levels and EV pPD-L1 in NSCLC patient samples (test cohort n=20, validation cohort n=45).
  • Correlated plasma biomarker levels with tumor PD-L1 TPS assessed via immunohistochemistry.
  • Main Results:

    • The MGS assay demonstrated high sensitivity for detecting EV pPD-L1.
    • EV pPD-L1 levels showed a strong linear correlation with tumor PD-L1 TPS in both test and validation cohorts (Pearson's r = 0.99).
    • Plasma PD-L1 levels, unlike EV pPD-L1, did not correlate with tumor PD-L1 TPS or EV pPD-L1.

    Conclusions:

    • Phosphorylated PD-L1 in plasma extracellular vesicles (EV pPD-L1) is a reliable biomarker for predicting tumor PD-L1 status in NSCLC.
    • The rapid MGS assay ( < 24h turnaround) can aid in selecting patients for PD-1/PD-L1 ICI therapy across all NSCLC stages.
    • Further validation in randomized controlled trials is warranted to integrate this liquid biopsy into routine clinical practice.
    lung cancer
    mesoporous material
    protein phosphorylation